R Flexsurv and time-dependent covariates - r

Question

I read that the R flexsurv package can also be used for modeling time-dependent covariates according to Christopher Jackson (2016) ["flexsurv: a platform for parametric survival modeling in R, Journal of Statistical Software, 70 (1)].
However, I was not able to figure out how, even after several adjustments and searches in online forums.
Before turning to the estimation of time-dependent covariates I tried to create a simple model with only time-independent covariates to test whether I specified the Surv object correctly. Here is a small example.
library(splitstackshape)
library(flexsurv)
## create sample data
n=50
set.seed(2)
t <- rpois(n,15)+1
x <- rnorm(n,t,5)
df <- data.frame(t,x)
df$id <- 1:n
df$rep <- df$t-1
Which looks like this:
t x id rep
1 12 17.696149 1 11
2 12 20.358094 2 11
3 11 2.058789 3 10
4 16 26.156213 4 15
5 13 9.484278 5 12
6 15 15.790824 6 14
...
And the long data:
long.df <- expandRows(df, "rep")
rep.vec<-c()
for(i in 1:n){
rep.vec <- c(rep.vec,1:(df[i,"t"]-1))
}
long.df$start <- rep.vec
long.df$stop <- rep.vec +1
long.df$censrec <- 0
long.df$censrec<-ifelse(long.df$stop==long.df$t,1,long.df$censrec)
Which looks like this:
t x id start stop censrec
1 12 17.69615 1 1 2 0
1.1 12 17.69615 1 2 3 0
1.2 12 17.69615 1 3 4 0
1.3 12 17.69615 1 4 5 0
1.4 12 17.69615 1 5 6 0
1.5 12 17.69615 1 6 7 0
1.6 12 17.69615 1 7 8 0
1.7 12 17.69615 1 8 9 0
1.8 12 17.69615 1 9 10 0
1.9 12 17.69615 1 10 11 0
1.10 12 17.69615 1 11 12 1
2 12 20.35809 2 1 2 0
...
Now I can estimate a simple Cox model to see whether it works:
coxph(Surv(t)~x,data=df)
This yields:
coef exp(coef) se(coef) z p
x -0.0588 0.9429 0.0260 -2.26 0.024
And in the long format:
coxph(Surv(start,stop,censrec)~x,data=long.df)
I get:
coef exp(coef) se(coef) z p
x -0.0588 0.9429 0.0260 -2.26 0.024
Taken together I conclude that my transformation into the long format was correct. Now, turning to the flexsurv framework:
flexsurvreg(Surv(time=t)~x,data=df, dist="weibull")
yields:
Estimates:
data mean est L95% U95% se exp(est) L95% U95%
shape NA 5.00086 4.05569 6.16631 0.53452 NA NA NA
scale NA 13.17215 11.27876 15.38338 1.04293 NA NA NA
x 15.13380 0.01522 0.00567 0.02477 0.00487 1.01534 1.00569 1.02508
But
flexsurvreg(Surv(start,stop,censrec) ~ x ,data=long.df, dist="weibull")
causes an error:
Error in flexsurvreg(Surv(start, stop, censrec) ~ x, data = long.df, dist = "weibull") :
Initial value for parameter 1 out of range
Would anyone happen to know the correct syntax for the latter Surv object? If you use the correct syntax, do you get the same estimates?
Thank you very much,
best,
David
===============
EDIT AFTER FEEDBACK FROM 42
===============
library(splitstackshape)
library(flexsurv)
x<-c(8.136527, 7.626712, 9.809122, 12.125973, 12.031536, 11.238394, 4.208863, 8.809854, 9.723636)
t<-c(2, 3, 13, 5, 7, 37 ,37, 9, 4)
df <- data.frame(t,x)
#transform into long format for time-dependent covariates
df$id <- 1:length(df$t)
df$rep <- df$t-1
long.df <- expandRows(df, "rep")
rep.vec<-c()
for(i in 1:length(df$t)){
rep.vec <- c(rep.vec,1:(df[i,"t"]-1))
}
long.df$start <- rep.vec
long.df$stop <- rep.vec +1
long.df$censrec <- 0
long.df$censrec<-ifelse(long.df$stop==long.df$t,1,long.df$censrec)
coxph(Surv(t)~x,data=df)
coxph(Surv(start,stop,censrec)~x,data=long.df)
flexsurvreg(Surv(time=t)~x,data=df, dist="weibull")
flexsurvreg(Surv(start,stop,censrec) ~ x ,data=long.df, dist="weibull",inits=c(shape=.1, scale=1))
Which yields the same estimates for both coxph models but
Call:
flexsurvreg(formula = Surv(time = t) ~ x, data = df, dist = "weibull")
Estimates:
data mean est L95% U95% se exp(est) L95% U95%
shape NA 1.0783 0.6608 1.7594 0.2694 NA NA NA
scale NA 27.7731 3.5548 216.9901 29.1309 NA NA NA
x 9.3012 -0.0813 -0.2922 0.1295 0.1076 0.9219 0.7466 1.1383
N = 9, Events: 9, Censored: 0
Total time at risk: 117
Log-likelihood = -31.77307, df = 3
AIC = 69.54614
and
Call:
flexsurvreg(formula = Surv(start, stop, censrec) ~ x, data = long.df,
dist = "weibull", inits = c(shape = 0.1, scale = 1))
Estimates:
data mean est L95% U95% se exp(est) L95% U95%
shape NA 0.8660 0.4054 1.8498 0.3353 NA NA NA
scale NA 24.0596 1.7628 328.3853 32.0840 NA NA NA
x 8.4958 -0.0912 -0.3563 0.1739 0.1353 0.9128 0.7003 1.1899
N = 108, Events: 9, Censored: 99
Total time at risk: 108
Log-likelihood = -30.97986, df = 3
AIC = 67.95973

Answer 1

Reading the error message:
Error in flexsurvreg(Surv(start, stop, censrec) ~ x, data = long.df, dist = "weibull", :
initial values must be a numeric vector
And then reading the help page, ?flexsurvreg, it seemed as though an attempt at setting values for inits to a named numeric vector should be attempted:
flexsurvreg(Surv(start,stop,censrec) ~ x ,data=long.df, dist="weibull", inits=c(shape=.1, scale=1))
Call:
flexsurvreg(formula = Surv(start, stop, censrec) ~ x, data = long.df,
dist = "weibull", inits = c(shape = 0.1, scale = 1))
Estimates:
data mean est L95% U95% se exp(est) L95% U95%
shape NA 5.00082 4.05560 6.16633 0.53454 NA NA NA
scale NA 13.17213 11.27871 15.38341 1.04294 NA NA NA
x 15.66145 0.01522 0.00567 0.02477 0.00487 1.01534 1.00569 1.02508
N = 715, Events: 50, Censored: 665
Total time at risk: 715
Log-likelihood = -131.5721, df = 3
AIC = 269.1443
Extremely similar results. My guess was basically a stab in the dark, so I have no guidance on how to make a choice if this had not succeeded other than to "expand the search."

Answer 2

I just want to mention that in flexsurv v1.1.1, running this code:
flexsurvreg(Surv(start,stop,censrec) ~ x ,data=long.df, dist="weibull")
doesn't return any errors. It also gives the same estimates as the non time-varying command
flexsurvreg(Surv(time=t)~x,data=df, dist="weibull")